The probability of HIV transmission depends on the interplay of many different factors related to infectivity of the HIV-infected partner, susceptibility of the HIV-uninfected partner, and biological characteristics of the virus. However, the interpretation of the available data linking transmissibility and viral and host factors is complex and incomplete. Not all HIV-exposed individuals become infected and some exposed individuals seem to require more exposure to become infected. Accumulated data suggest that some subtypes or strains of HIV have higher prevalence than others and may be more readily transmitted. The lack of transmission to some repeatedly exposed individuals has also been shown to be due to host related factors, including HLA background and chemokine receptor polymorphisms. The aims of this project are to characterize further the natural history, biology and molecular epidemiological features of HIV-1 strains prevalent in China and the host and viral factors which influence HIV-1 transmission and disease course. Being one integrated program, this project will use the cohorts built by Project 1 and social data generated in Project 2 to adjust the behavior influence while analyze the biological factors. This project will also develop reagents incorporating the predominant strains of HIV in China, which will be used for evaluating the immune status of Chinese HIV-infected patients and for developing and testing candidate AIDS vaccines, encoding subtype B'/C genes, being developed in Project5. This project will also characterize the CD8 T cell response in patients infected with B'/C virus and determine the extent of cross-clade reactivity with clade B and B' antigens. This kind of knowledge is critical for us to design effective prevention strategies, to predict the trend of the HIV-1 epidemic and to direct the design of new HIV vaccines for use in China. In accomplishing these aims, this project will also serve as a training ground for a cadre of young Chinese scientists with the knowledge and skills required to develop and evaluate strategies for preventing HIV infection. In particular, our specific aims are: 91) To identify viral and host factors that correlate with HIV transmission and disease progression in three IDU cohorts and one blood donor/DC cohort. (2) To develop reagents for assessing the cellular immune response to the predominant Chinese B'/C and B' subtype viruses and for testing candidate vaccines encoding Chinese gene products for efficacy in macaques. (3) To identify the immunodominant CTL epitopes and their MHC restricting elements in the most prevalent Chinese HIV subtypes and to evaluate the extent of cross-clade reactivity for help in designing vaccine strategies suitable to China.